Effects of negatively charged shift reagents on red blood cell morphology, lithium ion transport, and membrane potential

Abstract

Inorg. Chem. 1990,Li+ T , relaxation times presumably can be used as probes of Li' binding to the RBC membrane and for determining whether the extent and site of Li+ binding are different in RBCs from bipolar, hypertensive, and normotensive controls. Thus, the MIR approach (because of the its total noninvasiveness, easy visualization of Li+ pools, and ability to probe interactions between the Li' ion and RBC components) will be the method of choice to investigate whether Li+ transport and distribution parameters in RBCs can be used with confidence as genetic markers of bipolar disorder^)^ and h y p e r t e n~i o n .~~ 29. [3979][3980][3981][3982][3983][3984][3985] 3979 ( Received November 14, I989 Lanthanide shift reagents have been used extensively in multinuclear magnetic resonance (NMR) applications in order to obtain information regarding ion distribution and transport in cellular systems. The aqueous reagents used in this study were Dy(PPP)J-, Tm( PPP)J-, Dy(TTHA)'-, Dy(PcPcP);-, and Dy(DOTP)'-, where Dy3+ and Tm3+ represent dysprosium and thulium ions and PPPs-, TTHA6-, PcPcPs-, and DOTP*-denote the triphosphate, triethylenetetraminehexaacetate, bis(dihydroxyphosphiny1-methyl)phosphinate, and I ,4,7,1 O-tetrazacyclododecane-N,N',N",N"'-tetrakis(methanephosphonate) ligands, respectively. The apparent size and shape of Li+-free RBCs (red blood cells), studied by both scanning electron microscopy and Coulter counter methods, were unchanged by the presence of the above shift reagents at concentrations lower than 10 mM. However, Li+ incubation changed both the shape and size of RBCs. The rates of Na+-Li+ exchange in Li+-loaded RBCs measured by 7Li NMR spectroscopy in the presence of Dy(PPP);-, TI~(PPP),~-, or D~(PcPcP),~-were significantly higher than the rates measured in the absence of shift reagents by atomic absorption or in the presence of DY(TTHA)~-or DY(DOTP)~-by 7Li NMR spectroscopy. 31P and I9F NMR measurements of the membrane potential of Li+-free RBCs revealed that the shift reagents studied (except for Dy(TTHA)") do change the membrane potential, with the most negatively charged reagents having the largest effect. Thus, shift reagents must be used with caution in physiological NMR studies and in particular RBC applications.

Tmdotp5− as a 23na shift reagent for the in vivo rat kidney

“…1 (right panel), the single 23Na resonance broadened upon infusion of DyTTHA3 -, and the intracellular Nat resonance was visible only as a shoulder on the shifted extracellular Nat resonance after 3-5 mmole/kg BW of DyTTHA3-had been added. This SR dose was about [5][6][7][8] times higher than that required by TmDOTPS-to produce a comparable shift. A third highly shifted Na+ resonance could not be detected in any animal when using DyTTHA3 -.…”

“…Another measure of toxicity of an SR might be its rate of clearance from tissue. It has been shown previously that the chemical shift induced by an SR is proportional to its concentration (8). Therefore, the renal washout rate of TmDOTP5-was measured by monitoring the frequency of the '"Na resonance from the interstitial plus vascular space after stopping the SR infusion.…”

“…Infusion of either SR was initiated at a rate of 2 ml/h. After 3 min, the rate was gradually increased to 8 ml/h over a period of 6 min and then maintained at this level for 20 to 30 min. After achieving a chemical shift difference of 7-10 ppm between the intracellular and extracellular Na+ resonances, the infusion rate was reduced to 2-3 ml/h and maintained at this level for the duration of the experiment.…”

“…The normal saline was used to obtain control data while the 300 mM NaCl solution was infused to mimic the osmolality of 80 mM Na3H,TmDOTP~3NaOAc, Infusion of each of the three experimental solutions was initiated at a rate of 2 ml/h. After 3 min, the rate was gradually increased to 8 ml/h over a period of 6 min and then maintained at this rate for 20 min. The rate was then reduced to 3 ml/h and maintained for the duration of experiment.…”

Spectral, Electrochemical, Fluorescence, Kinetic and Anti-microbial Studies of Acyclic Schiff-base Gadolinium(III) Complexes

“…3 One of the most important applications is the use of Gd(III) complexes for magnetic resonance imaging (MRI) 4,5 anionic Gd(III) complexes are potentially useful as MRI contrast agents with low toxicity. 6 Mononuclear complexes of rare earth ions have considerable attention because of their electronic and nuclear properties which are of great interest in luminescent, 7 as a catalysts for RNA cleavage, 8 radioimmunotherapy, radioimmunoscintigraphy, as NMR shift reagents, 9,10 as NMR shift and relaxation agents for proteins 11 and biological cations and, luminescent computational logic gates.…”